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Biomedical subjects

J A Morris

Publications and source records attributed to J A Morris.

At least 145 records · Page 8Linked to original sources

Assessment of value of calibrated lyophilised plasmas to determine International Sensitivity Index for coagulometers.

An attempt was made to correct for the effects of coagulometers on the International Sensitivity Index (ISI) in a series of collaborative studies. Modified ISI were derived from the prothrombin time results with coagulometer systems using a range of calibrated plasmas. Two alternative approaches to correction of the ISI were evaluated. The first relied on the consensus orthogonal regression slopes of the prothrombin times for each coagulometer system plotted against the consensus manual results; the second depended on the local individual slope of the prothrombin times for each instrument. The two procedures were compared with the currently recommended method where International Normalised Ratios (INR) are derived from the manual ISI of the thromboplastin. The recommended method gave a significant bias from the manual results with most coagulometers. In contrast, the local correction procedure gave no significant biases, whereas the consensus method did so in a few instances. Both these correction procedures seem more reliable than the recommended method of INR derivation, but the local correction is more accurate and offers a more practical solution by allowing laboratories to determine their own corrected ISI on a range of calibrated plasmas.

Calibration↗

Staphylococcal toxins and sudden infant death syndrome.

AIMS: To investigate the hypothesis that commonly occurring bacterial toxins cause sudden infant death syndrome (SIDS) by (1), determining in which tissues bacterial toxins are concentrated after intravenous injection in rats; and (2), seeing if the same tissues contain detectable toxins in cases of SIDS. METHODS: The tissue distribution of intravenously injected staphylococcal enterotoxin A (SEA), enterotoxin B (SEB), enterotoxin C (SEC), enterotoxin D (SED), toxic shock syndrome toxin (TSST-1), and alpha-haemolysin was studied in rats using immunohistology and polyacrylamide gel electrophoresis with immunoblotting. Immunostaining was also carried out on formalin fixed kidneys from cases of SIDS and a comparison series of necropsy cases using anti-SEA, anti-SEB, anti-SEC2 and anti-SED. RESULTS: Immunohistology showed that SEB, SEC, SED and TSST-1 were all concentrated in the proximal convoluted tubular cells of the kidney. The presence of these toxins was confirmed in kidney homogenates using electrophoresis and immunoblotting. There was positive granular staining in the proximal convoluted tubular cells of the kidney in 36% of SIDS cases and 12% of the comparison series with anti SEC2 (chi 2 = 6; p < 0.025). CONCLUSION: SEC, or a bacterial toxin with epitopes in common, could have a pathogenic role in SIDS.

Animals↗

Lethal synergistic action of toxins of bacteria isolated from sudden infant death syndrome.

AIM: To test the hypothesis that lethal toxins of bacteria associated with sudden infant death syndrome (SIDS) can act synergistically. METHODS: Bacteria occurring together in the nasopharynx of cases of cot death were studied. The lethal toxicity of crude toxin preparations was determined over a range of dilutions by injections into the chorioallantoic vein of the chick embryo. Toxin preparations of low lethality for the chick embryo SIDS model were then tested in combination. RESULTS: Staphylococcus aureus toxin preparations showed low lethality when tested alone, even at low dilution. At 1 in 100 dilution S aureus toxin was lethal to one out of 15 chick embryos. Escherichia coli toxin preparations showed high lethality except on high dilution (1 in 80) when lethality fell to two out of 15 of chick embryos. When the same toxin preparations were tested simultaneously in combination, lethality rose to 14 out of 15. Similar findings were observed over a range of toxin dilutions. This finding was highly significant (p = 0.0012). CONCLUSIONS: That synergy between toxins can enhance the lethality of toxins elaborated by bacteria associated with SIDS.

Animals↗

Possibility of separating toxins from bacteria associated with sudden infant death syndrome using anion exchange chromatography.

AIMS: To develop techniques for the characterisation of toxins elaborated by a strain of Escherichia coli associated with sudden infant death syndrome (SIDS). METHODS: E coli SIDS 04, isolated from the nasopharynx of a case of SIDS, was studied. Cell-free toxin preparations were standardised, their protein measured, and analytical separation of proteins achieved using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Acetone precipitation of proteins was required prior to Coomassie blue staining of bands. Preparative separation was achieved on an anion exchange column using a programmed concentration gradient of NaCl in TRIS buffer. Fractions were tested individually or pooled for presence of lethal toxin including endotoxin. Lethal toxin was detected with the chick embryo test system. Endotoxin was measured using a chromogenic modification of the Limulus amoebocyte assay. RESULTS: Twenty one peaks were detected by chromatography. Ten individual, or pooled, fractions were assayed for endotoxin which ranged from 27-33 pg/ml. Much greater variation was found when the same fractions were assayed in chick embryos. E coli fractions varied considerably in lethal toxicity, from 0/10 to 10/10 chick embryos killed/tested. Certain E coli fractions tested individually (lethality four out of 10 to eight out of 10) proved more lethal (10 out of 10) if pooled prior to testing. CONCLUSIONS: In E coli infection associated with SIDS relatively low concentrations of extracellular protein are lethally toxigenic for the chick embryo model of SIDS. These proteins can be separated analytically by SDS-PAGE and preparatively by anion exchange chromatography. Toxicity of individual fractions is not correlated with endotoxin concentrations in samples tested.

Animals↗

Long-term follow-up of unsuccessful violent suicide attempts: risk factors for subsequent attempts.

STUDY POPULATION: Of 9046 consecutive trauma admissions, all suicide attempts (n = 156) were identified: 38 patients (24%) died in hospital; 118 (76%) were discharged and received long-term follow-up (mean = 2.8 years). Factors assessed included suicidal ideation and planning, reason for attempt; number of attempts, methods, dates of prior and subsequent attempts; psychiatric diagnoses, substance abuse history, treatment and medication compliance, hospitalizations, incidence of family depression and suicide; education level, job history, and living conditions. RESULTS: 104 (88%) patients were interviewed and 14 (12%) were lost to follow-up. Seventy-seven of the patients (74%) used guns in their attempt; their mean ISS was 14.2. Seven (6.7%) made repeat suicide attempts (all unsuccessful). Late mortality was 7% (one related to index suicide, five to chronic illness, one to motor vehicle crash). Most patients (96%) had psychiatric diagnoses at discharge, 77 of 93 (83%) had diagnosed depression. Sixty-six percent (69 of 104) had histories of alcohol abuse, 42% (42 of 101) histories of drug abuse. Thirty-five percent (34 of 96) were noncompliant with psychiatric follow-up and 70% (16 of 23) were noncompliant with alcohol abuse treatment. CONCLUSIONS: (1) Repeat attempts were rare (7%) after failed suicide attempts. (2) No late deaths resulted from repeat suicide attempts. (3) Risk factors associated with repeat attempts were younger age (p = 0.002), prior attempts (p = 0.02), family history of suicide (p = 0.03), schizophrenia (p = 0.005), and not living at home (p = 0.04). (4) Identifying patients with these risk factors, ensuring that they receive inpatient alcohol abuse treatment, along with sustained psychiatric treatment and help in maintaining home environments, may prevent repeat suicide attempts.

Adolescent↗

High-level positive end-expiratory pressure management in trauma-associated adult respiratory distress syndrome.

This study evaluated the effect of high-level positive end-expiratory pressure (PEEP) on mortality, barotrauma, intrapulmonary shunt (Qsp/Qt), and oxygen delivery (DO2) in posttraumatic adult respiratory distress syndrome (ARDS). All hypoxemic trauma patients admitted to the surgical intensive care unit (SICU) in 1989-1990 who received PEEP greater than 15 cm H2O were included. The PEEP was titrated to achieve an intrapulmonary shunt (Qsp/Qt) of approximately 0.20, and FIO2 was weaned to less than 0.50. Hemodynamic and pulmonary variables at four distinct intervals were recorded. Fifty-nine patients received PEEP greater than 15 cm H2O. Of these, 19 patients died of severe head injury or uncontrollable hemorrhage (16 within 48 hours). Forty (29 male, 11 female) were evaluated in detail. The PEEP levels ranged from 18-50 cm H2O with a mean of 27. PaO2/FIO2 ratios and Qsp/Qt improved as PEEP therapy was titrated. Cardiac index and oxygen delivery were maintained or improved throughout PEEP therapy by transfusion and fluid resuscitation, with a mean maximum positive fluid balance of 21.1 L and an average of 51 units of blood and blood products transfused per patients during their SICU stay. Twenty-nine (73%) had evidence of barotrauma, the majority being pneumothoraces clearly related to the initial trauma. Only three (7.5%) had evidence of barotrauma not related to trauma or line insertion. Eight of 40 patients (20%) died. Mean ISS and RTS for the entire group were 32 and 5.88, respectively. We conclude that titration of PEEP to achieve a Qsp/Qt of approximately 0.20 is an attainable goal. This was accomplished with minimal hemodynamic effects or barotrauma and a low mortality rate.

Adolescent↗

Hepatic enzyme response and hyperpyrexia after severe liver injury.

A multi-center experience with 210 severe liver injuries was reviewed to define postoperative changes in hepatic enzyme levels and body temperature profile. The 129 patients who survived initial operation comprised the data base. Serum glutamic oxaloacetic transaminase (SGOT) and lactate dehydrogenase (LDH) peaked within 24 hours (750 +/- 92 IU/L, 870 +/- 120 IU/L) and decreased rapidly during the first 4 days. Serum bilirubin was maximal at 7 days, while alkaline phosphatase rose slowly throughout 14 days. Hepatic enzyme elevations were more dramatic after blunt trauma, reflecting greater hepatocellular disruption. Maximum daily temperatures exceeding 38.0 degrees C and 39.0 degrees C were recorded for the first 3 postoperative days in 82 (64%) patients and 14 (11%) patients, respectively. No infectious source was evident in 13 (93%) of 14 patients with severe hyperpyrexia, implicating release of inflammatory mediators associated with major hepatic trauma. Convalescence from severe hepatic injury is marked by release of SGOT and LDH, as well as fever, which may be anticipated during the first 4 days postinjury.

Adult↗

Pediatric organ donation: the paradox of organ shortage despite the remarkable willingness of families to donate.

The 105 pediatric deaths (ages 1 to 16 years) that occurred at Vanderbilt University Medical Center during a 31-month period were reviewed to define the size of the donor pool in the pediatric population and to assess the role of physicians in the procurement of these much-needed organs. Computerized discharge abstracts showed that 57 pediatric patients died without contraindications to organ donation. Manual review of these 57 medical records yielded 46 records suitable for review by Tennessee Donor Services. From this group, 19 eligible donors were identified. All eligible donors died from trauma, intracerebral hemorrhage, anoxic events, or hydrocephalus. Physicians failed to ask one family for permission to donate. All 18 of the families who were asked agreed to donate and organs were successfully procured from all 18 patients. These data suggest that families of pediatric patients are much more willing to agree to donation than the families of adult patients. As a result of this study, a simplified audit process has been developed for hospitals to use in evaluating compliance with required-request legislation.

Adolescent↗

Trauma in pregnancy. Predicting pregnancy outcome.

A multicenter study involving three American College of Surgeons Level 1 trauma centers was undertaken to assess parameters that may predict fetal outcome. The records of 93 injured pregnant patients admitted from April 1, 1985, to March 31, 1990, were reviewed. There were three maternal deaths (3%) (mean Injury Severity Score, 43). Fourteen fetal/neonatal deaths (15%) occurred during the acute care admission period. Of these, eight were fetal deaths (two associated with maternal death), four were cases of elective abortions, and two were neonatal deaths. In general, the maternal physiologic and laboratory parameters assessed failed to accurately predict pregnancy outcome, while Injury Severity Score did differ significantly between patients whose pregnancies were viable (Injury Severity Score = 6.2) and those whose pregnancies were nonviable (Injury Severity Score = 21.6). Unique to this study were the findings that the Glasgow Coma Score also differed significantly in patients with viable (Glasgow Coma Score, 14.5) and nonviable (Glasgow Coma Score, 12.0) pregnancies, while fetal heart rate at admission to the emergency department did not. In this study, the incidence of fetal death was increased following direct uteroplacental fetal injury (100% of cases), maternal shock (67%), pelvic fracture (57%), severe head injury (56%), and hypoxia (33%). The adequacy of noninvasive maternal monitoring in assessing fetal well-being is challenged, and a discussion of diagnostic modalities for assessment for the injured gravida is set forth.

Accidents, Traffic↗

Prehospital diagnosis and treatment of acute myocardial infarction: a north-south perspective. The Cincinnati Heart Project and the Nashville Prehospital TPA Trial.

Intravenous thrombolytic therapy improves left ventricular function and reduces mortality in patients with acute myocardial infarction (AMI). In European and Middle Eastern trials, prehospital delivery of thrombolytic agents by physician-directed mobile intensive care units has been successful. This report describes two independently conceived and performed trials that used cellular telephone transmission of 12-lead ECGs to deliver recombinant tissue plasminogen activator (r-tPA) in the field to patients with AMI. In the Nashville Prehospital TPA Trial, 85 patients with chest pain were evaluated in the field for possible administration of r-tPA over a 6-month period. Three of 85 patients (3.5%) were found to be actual candidates for r-tPA treatment in the field. In phase II (dry-run phase) of the Cincinnati Heart Project, 374 patients were evaluated in the field with 14 documented cases of AMI (3.7%) before r-tPA was placed in ambulances for administration by paramedics. In phase III (active with r-TPA in ambulances), over a 1-year period 103 patients were evaluated with six (5.8%) documented cases of AMI. Three of five r-tPA field treatment decisions by emergency physicians using transmitted 12-lead ECGs were accurate (60%). When patients in phases II and III were combined, only 20 of 477 total patients (4.2%) were documented to have AMI. A decline in paramedic skills was noted because of the infrequent administration of the thrombolytic agent. Combining the Nashville and Cincinnati experiences, only 27 of 562 total patients with chest pain (4.8%) were candidates for prehospital thrombolysis. We conclude that few patients evaluated in the prehospital setting are actual candidates for thrombolytic therapy. Substantial allocation of financial and human resources for prehospital delivery of intravenous thrombolytic therapy does not appear warranted.

Adolescent↗

Combination thrombolytic therapy: a comparison of simultaneous and sequential regimens of tissue plasminogen activator and urokinase.

Coronary angioplasty following unsuccessful tissue plasminogen activator (t-PA) therapy for acute myocardial infarction has been associated with a high incidence of subsequent reocclusion of the infarct-related artery, and a relatively high in-hospital mortality. In contrast, the combination of t-PA and urokinase, when given intravenously prior to coronary angiography, appears to be associated with a low incidence of post-rescue angioplasty reocclusion. In order to determine whether intraprocedural urokinase, given at the time of rescue coronary angioplasty for failed t-PA therapy, improves long-term patency of the infarct vessel to the same extent as preangiographic, combination t-PA/urokinase therapy, three thrombolytic treatment strategies were retrospectively compared. The first group included 86 patients undergoing rescue angioplasty after t-PA monotherapy (t-PA alone). The clinical and angiographic outcomes of these patients were compared with those of 24 patients who received intravenous or intracoronary urokinase during rescue angioplasty following unsuccessful t-PA therapy (sequential t-PA/urokinase therapy), and with those of 34 patients undergoing rescue coronary angioplasty following unsuccessful therapy with the combination of intravenous t-PA and urokinase (simultaneous therapy). There was no difference in postangioplasty patency rate of the infarct-related artery between the three groups. However, the sequential t-PA/urokinase regimen was associated with a subsequent reocclusion rate that was lower than the rate that occurred in the t-PA monotherapy group but higher than the rate in the simultaneous t-PA/urokinase group (13 versus 29 versus 2%, respectively; p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗

Age-associated changes in neuroaxonal transport in the hypothalamo-neurohypophysial system of the mouse.

In this study, we investigated age-associated changes in neuroaxonal transport of the hormone vasopressin (AVP) and its associated neurophysin (NPII), from the supraoptic nucleus (SON) of the hypothalamus to the neurohypophysis. C57BL/Icrfat male mice of 6 and 28 months of age were injected in the hypothalamus with L-[35S]cysteine. Animals were killed up to 2.25 h after injection and NPII and AVP from the SON and neurohypophysis were separated using HPLC, and the fractions counted for radioactivity. In the SON, radiolabelled NPII and AVP were first detected after 0.50 h in both young and old mice. There was no significant difference between the age-groups in the incorporation of radiolabel over the time course studied. Radiolabelled NPII in the neurohypophysis was significantly above background after 1.25 h in the young, and after 1.50 h in the old mice. The differences between the two age groups was significant (P = 0.05). Radiolabelled AVP followed a similar trend, but was not significantly above background until 1.50 h in the young and 1.75 h in the old. The differences between the two age groups was on the point of significance (P = 0.056). These results indicate a significant reduction of up to 25% in the rate of axonal transport of neurohypophyseal peptides with advancing age.

Aging↗

The age incidence of childhood acute lymphoblastic leukaemia.

A mathematical model of childhood acute lymphoblastic leukaemia (ALL) is presented which is based on the assumptions that: 1) malignant clones of lymphoblasts arise by spontaneous mutation; 2) this is normally prevented by repair systems which either cause intracellular DNA repair or eliminate the malignant clone; and 3) the repair systems are fallible and their performance decays at random with time. If the major drive to lymphocyte division is microbial antigens then the model produces a reasonable fit to published data on the age distribution of ALL. Furthermore the model offers an explanation for the apparent increase in the incidence of ALL which is associated with improved social conditions.

Adolescent↗

Evaluating quality, cost-effective health care. Vascular database predicated on hospital discharge abstracts.

This population-based study examines all carotid endarterectomies (CE) performed by all surgeons in a single state over a 10-year period. The methodology is designed to determine morbidity rate, mortality rate, cost, and length of stay, as well as to understand the effect of pre-existing chronic disease, physician, and hospital volume on these outcome variables. The data source consisted of hospital discharge abstract data uniformly collected on all admissions (N = 5.9 million) to acute care hospitals in the state. In the decade 1979 to 1988, 11,199 patients underwent CE. Mortality rate from CE was 2.1%, and the postoperative stroke rate was 3.7% over this period. High physician volume decreased the mortality rate (p less than 0.05) and stroke rate (p less than 0.01) by 50% and significantly (p less than 0.001) reduced hospital cost and length of stay independent of patient complexity. Examination of cost data, adjusted for inflation, showed a decrease in mean cost for CE over the decade. Thus physicians are providing better care for less hospital dollars. Both patient and payor outcome is improved by concentrating CE patients in the hands of high-volume surgeons. Although the data suggests this trend is already evolving, the pace of this evolution can be expected to increase as payors recognize that regionalization of this procedure lowers costs.

Arteriosclerosis↗

Trauma patients return to productivity.

Economic issues threaten the development of a national trauma system. Much work has focused on the cost of trauma care; little has been done to define society's long-term economic return. We asked three questions about high cost trauma patients: (1) Do they survive?, (2) Do they continue to require expensive care?, and (3) Do they return to productivity? Of 6,129 consecutive trauma admissions, 114 had hospital charges over $100,000 (mean = $143,000), 102 (89.5%) were discharged alive, and 10 (8.8%) were lost to followup. Ninety-two patients or families were interviewed at least 1 year (mean = 2.6 year) after discharge. There were 88 survivors and 4 deaths (3.5%). Of the 88 survivors 73% had no limitation of ADLs, 67% received rehabilitation, 58% were still improving, and 37% were involved in litigation. Five survivors (5.7%) were confined to a nursing home, 48 (54.5%) had returned to productivity (RTP), 35 (39.8%) were unemployed, and five of these still require medical therapy. We conclude: (1) The majority of high cost patients survive (89.5%) and return to productivity (54.5%); (2) the severity of injury predicts survival but not return to productivity; and (3) the RTP rate may be increased by addressing nonmedical need.

Activities of Daily Living↗